title: IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma.
abstract: IL-17 is a pivotal proinflammatory molecule in asthmatics. However, the cellular source of IL-17 in asthma has not been identified to date. In this study, we report that macrophages rather than Th17 cells are the main producer of IL-17 in allergic inflammation related to asthma. After OVA challenge in a mouse model mimicking allergic asthma, the increased IL-17(+) cells in the lung were mainly CD11b(+)F4/80(+) macrophages, instead of T cells or others. Importantly, IL-17(+) alveolar macrophages (AMs), but not IL-17(+) interstitial macrophages, were significantly increased after allergen challenge. The increase of IL-17(+) AMs was not due to the influx of IL-17(+) macrophages from circulation or other tissues, but ascribed to the activation of AMs by mediator(s) secreted by IgE/OVA-activated mast cells. Depleting alveolar macrophages or neutralizing IL-17 prevented the initiation of OVA-induced asthma-related inflammation by inhibiting the increase of inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid. Th2 cytokine IL-10 could down-regulate IL-17 expression in alveolar macrophages. The increased IL-17 and the decreased IL-10 in bronchoalveolar lavage fluid were further confirmed in asthmatic patients. These findings suggest that IL-17 is mainly produced by macrophages but not Th17 cells in allergic inflammation related to asthma. Mast cell-released mediators up-regulate the expression of IL-17 by macrophages, whereas IL-10 down-regulates IL-17 expression.
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China.
authors.forename: Chuanwang
authors.initials: C
authors.lastname: Song
authors.forename: Liqiong
authors.initials: L
authors.lastname: Luo
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lei
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Guimei
authors.initials: G
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Zuo-Hua
authors.initials: ZH
authors.lastname: Feng
mesh_terms: D000208:Acute Disease; D000328:Adult; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D039481:CD11b Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D020381:Interleukin-17; C036763:monocyte-macrophage differentiation antigen